Arina Nikitina, Andre Norfleet, Eunbi Park, Daniel Cruz, Jack Toppen
Collaborators: Elena Dimitrova (Cal Poly), Facundo Fernandez (Georgia Tech), Todd McDevitt, (Gladstone), Calin Belta (BU), Ron Weiss (MIT)
Funding Sources: NSF Emergent Behavior of Integrated Cellular Systems (EBICS) Science & Technology Center, NSF-Simons Foundation Southeast Center for Mathematics & and Biology, NSF Cell Manufacturing Technologies (CMaT) Engineering Research Center
Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into cell types of all germ lineages, making them a potentially robust cell source for regenerative medicine therapies; however, the fate and behavior of ESCs is difficult to control and predict, which currently limits their potential uses in medicine and industry. Two projects currently underway:
Gap junction-mediated intercellular communication can affect differentiation in a spatiotemporal manner. Using both experimental and computational tools, we can investigate how heterogeneity in the intercellular network can lead to intracellular gradients within multicellular systems, thus modulating susceptibility to differentiation cues. Furthermore, the use of computational tools provides a means to quickly interrogate perturbations to the network and identify promising experimental conditions for deriving specific differentiation patterns.
We are also investigating metabolic regulation of stem cell differentiation to either decrease or control heterogeneity in multicellular systems. Recent findings suggest that metabolic changes that occur during stem cell differentiation potentially drive changes in gene regulatory networks and we hypothesize that this can be used to better control stem cell fate. We developed a protocol to collect matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) data on stem cell colonies and these are co-registered with confocal microscopy images to understand spatiotemporal control of differentiation.
Glen, C.M., Kemp, M.L., Voit, E.O. “Agent-based modeling of morphogenetic systems: Advantages and challenges”. PLoS Comput Biol, 15(3): e1006577. doi: 10.1371/journal.pcbi.1006577, 2019.
Kamm, R.D, Bashir, R., Arora, N., Dar, R.D., Gillette, M.U., Griffith, L.G., Kemp, M.L., Kinlaw, K., Levin, M., Martin, A.C., McDevitt, T.C., Nerem, R.M., Powers, M.J., Saif, T.A., Sharpe, J., Takayama, S., Takeuchi, S., Weiss, R., Ye, K., Yevick, H.G., Zaman, M.H. “Perspective: The promise of multi-cellular engineered living systems”. APL Bioengineering, 2(4): 040901. doi: 10.1063/1.5038337, 2018.
Glen, C.M., McDevitt, T.C., Kemp, M.L. “Dynamic intercellular transport modulates the spatial patterning of differentiation during early neural commitment”. Nature Communications, 9(1): 4111. doi: 10.1038/s41467-018-06693-1, 2018.
White, D.E., Sylvester J.B., Kinney M.A., Levario T.J., Lu, H., Streelman J.T., McDevitt, T.C., Kemp, M.L. “Quantitative Multivariate Analysis of Dynamic Multicellular Morphogenic Trajectories”, Integrative Biology, DOI:10.1039/c5ib00072f, 2015.
White, D.E., Kinney, M.A., McDevitt, T.C., Kemp, M.L. “Spatial Pattern Dynamics of 3D Stem Cell Differentiation via Rules-Based Computational Modeling”. PLoS Computational Biology, 9(3): e1002952, 2013.
Nair, R., Ngangan, A.V., Kemp, M.L., McDevitt, T.C. “Gene Expression Signatures of Extracellular Matrix and Growth Factors During Embryonic Stem Cell Differentiation”. PLoS One, 7(10): e42580, 2012.